The protein matrix in the center of the lens, while established early in life, remains present throughout life. Under these conditions even the slightest trace of proteolytic activity could lead to the destruction of this matrix, and may result in the formation of a lens opacity or cataract. The lens have been shown to contain several different trypsin-like enzymes, but these exist in the dormant state. This dormancy may represent the effect of an efficient trypsin inhibitor activity in the lens. We have shown the presence of several different trypsin inhibitors in the lens. The bulk of this inhibitor activity is due to one of the major lens structural proteins, alpha-crystallin. This multi-submit protein is able to inhibit several molecules of trypsin for each alpha-crystallin molecule. Alpha-crystallin can bind several different proteinases but this binding is remarkably sensitive to salt concentration. The properties of alpha-crystallin as a control molecule for proteolysis in the lens will be studied. The structural properties of alpha-crystallin will be determined under a variety of conditions and correlated with proteinase inhibitor activity. The proteinase binding site will be determined by modification of alpha-crystallin, iodination of the exposed proteinase surfaces in the complex, and crosslinking to adjacent subunits. It is known that with aging, alpha-crystallin is converted into a water insoluble form. Since solubilization of this protein fraction and has been accomplished, it will be possible to investigate the structure and inhibitor activity of the modified alpha-crystallin. All of these processes will be investigated for control mechanisms which could be correlated with the levels of free and bound cations in the aging human lens and in cataracts. It is proposed that alterations in the tertiary structure of alpha- crystallin promote aggregation. This process involves electrostatic interactions between protein molecules, leading to the exclusion of salt and water. The aggregated alpha-crystallin is no longer capable of inhibiting proteinase molecules and the increased salt concentration diminishes the inhibiting proteinase molecules and the increased salt concentration diminishes the inhibitor activity of the remaining alpha-crystallin. These conditions eventually lead to the presence of active proteinases in the lens which cause the autolysis of lens proteins seen in cataracts.